10-104050642-T-C

Position:

chr10-104050642-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000494.4(COL17A1):c.2107A>G(p.Met703Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,613,354 control chromosomes in the GnomAD database, including 522,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41598 hom., cov: 31)

Exomes 𝑓: 0.81 ( 481225 hom. )

Consequence

COL17A1
NM_000494.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.188

Variant links:

Genes affected

COL17A1 (HGNC:2194): (collagen type XVII alpha 1 chain) This gene encodes the alpha chain of type XVII collagen. Unlike most collagens, collagen XVII is a transmembrane protein. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form. [provided by RefSeq, Jul 2008]

COL17A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5010075E-6).

BP6

Variant 10-104050642-T-C is Benign according to our data. Variant chr10-104050642-T-C is described in ClinVar as [Benign]. Clinvar id is 256267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104050642-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.2107A>G	p.Met703Val	missense_variant	27/56	ENST00000648076.2	NP_000485.3	Q9UMD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2 linkuse as main transcript	c.2107A>G	p.Met703Val	missense_variant	27/56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.2107A>G	p.Met703Val	missense_variant	26/51	5		ENSP00000358748.3		Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110640

AN:

151924

Hom.:

41602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.799

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.766

GnomAD3 exomes

AF:

0.785

AC:

197385

AN:

251486

Hom.:

78408

AF XY:

0.787

AC XY:

107008

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.829

Gnomad ASJ exome

AF:

0.803

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.757

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.810

AC:

1182935

AN:

1461312

Hom.:

481225

Cov.:

100

AF XY:

0.809

AC XY:

587897

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.806

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.762

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.827

Gnomad4 OTH exome

AF:

0.793

GnomAD4 genome

AF:

0.728

AC:

110662

AN:

152042

Hom.:

41598

Cov.:

AF XY:

0.727

AC XY:

53993

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.799

Gnomad4 ASJ

AF:

0.814

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.760

Alfa

AF:

0.802

Hom.:

106605

Bravo

AF:

0.724

TwinsUK

AF:

0.832

AC:

3084

ALSPAC

AF:

0.831

AC:

3204

ESP6500AA

AF:

0.525

AC:

2313

ESP6500EA

AF:

0.818

AC:

7039

ExAC

AF:

0.780

AC:

94732

Asia WGS

AF:

0.690

AC:

2400

AN:

3478

EpiCase

AF:

0.826

EpiControl

AF:

0.821

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epithelial recurrent erosion dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.8

DANN

Benign

0.72

DEOGEN2

Benign

0.20

.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.36

T;.;T

MetaRNN

Benign

0.0000075

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.080

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.93

N;N;.

REVEL

Benign

0.22

Sift

Benign

0.56

T;T;.

Sift4G

Benign

0.29

T;T;.

Polyphen

0.0

.;B;B

Vest4

0.077

MPC

0.067

ClinPred

0.0010

GERP RS

-4.2

Varity_R

0.049

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over